Apigenin inhibits fibrous scar formation after acute spinal cord injury through TGFβ/SMADs signaling pathway

CNS Neurosci Ther. 2022 Nov;28(11):1883-1894. doi: 10.1111/cns.13929. Epub 2022 Jul 30.

Abstract

Aim: To investigate the effect of apigenin on fibrous scar formation after mouse spinal cord injury (SCI).

Methods: The pneumatic impactor strike method was used to establish an SCI model. Mice were intraperitoneally injected with 5 mg/kg or 20 mg/kg apigenin daily for 28 days after SCI. The Basso Mouse Scale (BMS) score, hematoxylin-eosin staining, and immunohistochemical staining were used to assess the effect of apigenin on scar formation and motor function recovery. Western blotting and qRT-PCR were used to detect the expression of fibrosis-related parameters in spinal cord tissue homogenates. NIH-3 T3 cells and mouse primary spinal cord fibroblasts, α-Smooth muscle actin (α-SMA), collagen 1, and fibronectin were used to evaluate apigenin's effect in vitro. Western blotting and immunofluorescence techniques were used to study the effect of apigenin on TGFβ/SMADs signaling.

Results: Apigenin inhibited fibrous scar formation in the mouse spinal cord and promoted the recovery of motor function. It reduced the expression of fibroblast-related parameters and increased the content of nerve growth factor in vivo, decreasing myofibroblast activation and collagen fiber formation by inhibiting TGFβ-induced SMAD2/3 phosphorylation and nuclear translocation in vitro.

Conclusion: Apigenin inhibits fibrous scar formation after SCI by decreasing fibrosis-related factor expression through TGFβ/SMADs signaling.

Keywords: TGFβ/SMADs; apigenin; fibrous scar; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Apigenin / pharmacology
  • Apigenin / therapeutic use
  • Cicatrix* / drug therapy
  • Cicatrix* / etiology
  • Cicatrix* / metabolism
  • Collagen / metabolism
  • Collagen / pharmacology
  • Eosine Yellowish-(YS) / metabolism
  • Eosine Yellowish-(YS) / pharmacology
  • Fibronectins / metabolism
  • Fibronectins / pharmacology
  • Hematoxylin / metabolism
  • Hematoxylin / pharmacology
  • Mice
  • Nerve Growth Factors / metabolism
  • Recovery of Function
  • Signal Transduction
  • Spinal Cord / pathology
  • Spinal Cord Injuries* / complications
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology

Substances

  • Actins
  • Fibronectins
  • Nerve Growth Factors
  • Transforming Growth Factor beta
  • Apigenin
  • Collagen
  • Eosine Yellowish-(YS)
  • Hematoxylin